1. Field of the Invention
The present invention relates to a method of measurement in biological systems. More particularly, it relates to a method of quantifying molecular mixtures of and adhesions to minute amounts of biological substances using an accelerator mass spectrometer. Still more particularly, it relates to a process of measurement using intermediate and long lived isotopes bound to biological substances which are then converted to forms suitable for analysis by accelerator mass spectrometry.
2. Background of the Invention
Isotopes of various elements, particularly .sup.14 C, have been used in biological processes for some time as a means of tracing, to determine fate and speeds of reaction processes, and for other purposes.
The measurements are made by scintillation counters, autoradiography or other devices which measure the amount of decay of isotopes which have a relatively short half life.
These methods, in general, cannot be used where human beings are involved because of the potential radiation damage from the isotopes and the amount of sample required. At radiation levels which are not harmful to humans, decay counting methods are insufficiently specific and sensitive to give meaningful results. Moreover, the background contamination is high, creating problems for the users of the equipment.
3. The Prior Art
A suggested solution of overcoming the problems associated with the use of short half life isotopes is to use an accelerator mass spectrometer.
As described by D. Elmore in an article in Biological Trace Element Research, Vol. 12, 1987, accelerator mass spectrometers can be used for a variety of purposes using long-lived radioisotopes. Such purposes include the introduction of isotopes as a tracer, then chemically processing the bulk tissue samples.
U.S. Pat. No. 4,037,100 describes an apparatus which can be used for the detection of electronegative particles and provide data as to their elemental composition. The apparatus includes an accelerator mass spectrometer (AMS) which can be used for making mass and elemental analyses. Still other references to AMS devices, and their uses include: Kilius et. al, "Separation of .sup.26 AL and .sup.26 Mg Isobars by Negative Ion Mass Spectrometry," Nature, Vol. 282, November 1979; A. E. Litherland, "Acceleration Mass Spectrometry," Nuclear Instruments and Methods in Physics Research B5, pp. 100-108, (1984); L. Brown, "Applications of Accelerator Mass Spectrometry," Ann. Rev. Earth Planet. Sci., Vol. 12, pp. 39-59, (1984); and A. E. Litherland, "Ultrasensitive Mass Spectrometry with Accelerators," Ann. Rev. Nucl. Part. Sci., Vol. 30, pp. 437-473, (1980).
Accelerator mass spectrometry (AMS) was developed as a highly sensitive method for counting long-lived but rare cosmogenic isotopes, typically those having half-lives between 10.sup.3 and 2.times.10.sup.7 years. Isotopes with this range of half-lives are too long-lived to detect easily by conventional decay counting techniques but are too short-lived on geological timescales to be present in appreciable concentrations in the biosphere or lithosphere. Assay of these cosmogenic isotopes (.sup.10 Be, .sup.14 C, .sup.26 Al, .sup.41 Ca, .sup.36 Cl, and .sup.129 I) by AMS has become a fundamental tool in archaeology, oceanography, and the geosciences, but has not been applied to problems of a biological or clinical nature.
It is an object of this invention to provide a method of biological analyses which is more specific than prior art methods.
It is a further object of this invention to provide a method of quantitive biological analysis which is more sensitive than methods known heretofore.
It is a still further object of this invention to provide a method of quantifying molecular mixtures of and adhesions to minute amounts of biological substances.
It is yet another object of this invention to provide a method of quantitive biological analysis using rare stable isotopes.
Another object of the invention is to provide a technique to measure the concentrations of long-lived radioisotopes at levels of a few parts in 10.sup.15 to parts in 10.sup.8 which can signal the presence or effects of very small amounts of labeled exogenous biochemicals within biological systems, organs, fluids, cells or parts of cells of living hosts, including humans.
Another object of the invention is to provide a technique to measure the concentrations of long-lived radioisotopes from within biological systems which does not make use of the radioactive decay of these isotopes.
Another object of the invention is to provide a technique to quantify the amount of an exogenous biochemical or several parts of an exogenous biochemical which have become adhered to or mixed with the natural biochemicals of a biological system using long-lived, radioactive molecular labels which are too low in concentration to be detected using techniques which depend on the decay of the radioisotopes.
Another object of the invention is to provide a technique to measure the concentrations of long-lived radioisotopes from within biological systems in which the labeled exogenous biochemical is stable over periods of time which are long compared to the period of biological effectiveness.
Another object of the invention is to provide a technique to measure the concentrations of long-lived radioisotopes from within biological systems in which the labeled exogenous biochemical is a close analogue of the natural, unlabeled form of the biochemical and without resort to the substitution of elements within the biochemical by short-lived radioisotopes of other similar elements or chemically labile short-lived radioisotopes.
Still another object of the invention is to provide a technique to measure the concentration of long-lived radioisotopes from within biological systems which represent molecular events whose probability is so low that natural levels of radioisotopes would mask the radioisotope labels attached to the exogenous effector.
These and other objects of the invention will be realized in the description, drawings, and claims to follow.